The present invention relates to pharmaceutical compositions. More particularly, the invention concerns novel compositions in which ester-containing .beta.-blocking drugs are stabilized against hydrolysis during shipping and storage.
In the past, the emphasis in .beta.-blocker research has been to develop stable drugs which could be administered to cardiac patients over relatively long periods of time. However, it is often desirable in the critical care setting to quickly reduce heart work or improve rhythmicity during a cardiac crisis, e.g., during or shortly after a myocardial infarction. Conventional .beta.-blocking agents can be employed for such treatment, but their long durations of action can cause undesirable side effects.
Recently, certain compounds containing ester functions have been found to possess .beta.-adrenergic blocking activity. (See U.S. Pat. No. 4,387,103 to Erhardt, et al., June 7, 1983, and U.S. Pat. No. 4,593,119, June 3, 1986.) These compounds generally have a short duration of action in vivo, and do not possess the disadvantages of the conventional .beta.-blockers described above. The ester groups in these compounds have, however, been found to be somewhat unstable in aqueous environments, such as intravenous infusion solutions. The practical effect of this instability is that conventional compositions containing the compounds have relatively short shelf lives, thus making commercial distribution and storage difficult.
Therefore, there remains a need for pharmaceutical preparations of short-acting .beta.-blockers which are stable in vitro and have a relatively long storage life.